イチハラ　アツヒロ   ICHIHARA Atsuhiro   市原　淳弘    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The role of individual domains and the significance of shedding of ATP6AP2/(pro)renin receptor in vacuolar H(+)-ATPase biogenesis.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：1932-6203(Electronic)1932-6203(Linking)
巻・号・頁	8(11),pp.e78603
著者・共著者	KINOUCHI Kenichiro†, ICHIHARA Atsuhiro*, SANO Motoaki, SUN-WADA Ge-Hong, WADA Yoh, OCHI Hiroki, FUKUDA Toru, BOKUDA Kanako, KUROSAWA Hideaki, YOSHIDA Naohiro, TAKEDA Shu, FUKUDA Keiichi, ITOH Hiroshi
担当区分	責任著者
発行年月	2013/02
概要	The ATPase 6 accessory protein 2 (ATP6AP2)/(pro)renin receptor (PRR) is essential for the biogenesis of active vacuolar H(+)-ATPase (V-ATPase). Genetic deletion of ATP6AP2/PRR causes V-ATPase dysfunction and compromises vesicular acidification. Here, we characterized the domains of ATP6AP2/PRR involved in active V-ATPase biogenesis. Three forms of ATP6AP2/PRR were found intracellularly: full-length protein and the N- and C-terminal fragments of furin cleavage products, with the N-terminal fragment secreted extracellularly. Genetic deletion of ATP6AP2/PRR did not affect the protein stability of V-ATPase subunits. The extracellular domain (ECD) and transmembrane domain (TM) of ATP6AP2/PRR were indispensable for the biogenesis of active V-ATPase. A deletion mutant of ATP6AP2/PRR, which lacks exon 4-encoded amino acids inside the ECD (Δ4M) and causes X-linked mental retardation Hedera type (MRXSH) and X-linked parkinsonism with spasticity (XPDS) in humans, was defective as a V-ATPase-associated protein. Prorenin had no effect on the biogenesis of active V-ATPase. The cleavage of ATP6AP2/PRR by furin seemed also dispensable for the biogenesis of active V-ATPase. We conclude that the N-terminal ECD of ATP6AP2/PRR, which is also involved in binding to prorenin or renin, is required for the biogenesis of active V-ATPase. The V-ATPase assembly occurs prior to its delivery to the trans-Golgi network and hence shedding of ATP6AP2/PRR would not affect the biogenesis of active V-ATPase.
DOI	10.1371/journal.pone.0078603
文献番号	24223829